Sequential Treatment of Estrogen Deficient, Osteopenic Rats with Alendronate, Parathyroid Hormone (1–34), or Raloxifene Alters Cortical Bone Mineral and Matrix Composition

Abstract

Anti-resorptive and anabolic treatments can be used sequentially to treat osteoporosis, but their effects on bone composition are incompletely understood. Osteocytes may influence bone tissue composition with sequential therapies because bisphosphonates diffuse into the canalicular network and anabolic treatments increase osteocyte lacunar size. Cortical bone composition of osteopenic, ovariectomized (OVX) rats was compared to that of Sham-operated rats and OVX rats given monotherapy or sequential regimens of single approved anti-osteoporosis medications. Adult female Sprague-Dawley rats were OVX (N = 37) or Sham-OVXd (N = 6). After 2 months, seven groups of OVX rats were given three consecutive 3-month periods of treatment with vehicle (V), h-PTH (1-34) (P), alendronate (A), or raloxifene (R), using the following orders: VVV, PVV, RRR, RPR, AAA, AVA, and APA. Compositional properties around osteocyte lacunae of the left tibial cortex were assessed from Raman spectra in perilacunar and non-perilacunar bone matrix regions. Sequential treatments involving parathyroid hormone (PTH) caused lower mean collagen maturity relative to monotherapies. Mean mineral:matrix ratio was 2.2% greater, mean collagen maturity was 1.4% greater, and mean carbonate:phosphate ratio was 2.2% lower in the perilacunar than in the non-perilacunar bone matrix region (all P < 0.05). These data demonstrate cortical bone tissue composition differences around osteocytes caused by sequential treatment with anti-osteoporosis medications. We speculate that the region-specific differences demonstrate the ability of osteocytes to alter bone tissue composition adjacent to lacunae.

The relative contribution of bone microarchitecture and matrix composition to implant fixation strength in rats

“…Bone matrix composition is altered in prevalent diseases relevant to orthopedic surgery such as osteoporosis and type 2 diabetes mellitus (T2DM). While osteoporosis is mainly thought of as a disease of low bone mineral density, both preclinical 5 and clinical observation studies 6–9 have demonstrated that bone matrix composition is also altered by osteoporosis and these alterations contribute to fragility fracture risk 10 . T2DM is another condition known to change bone matrix composition in preclinical 11 and clinical studies, 12,13 which likely contribute to the elevated rates of fragility fracture despite normal bone mineral density 14,15 …”

Raloxifene Ameliorates Glucosamine-Induced Insulin Resistance in Ovariectomized Rats

“…Selective estrogen receptor modulators (SERMs) act on estrogen receptors with agonist or antagonist activity, depending on the tissue type. Raloxifene (RLX) is an SERM used for the treatment of postmenopausal osteoporosis (OP) because of its activity as an estrogen receptor agonist in bone [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. The effect of RLX can be tissue- or species-specific [ 29 ].…”

Effect of flaxseed oil on biochemical parameters, hormonal indexes and stereological changes in ovariectomized rats

“…Ovariectomy is well known to decreased oestrogen hormones, calcium metabolism, bone mineral content, endometrial and lumen weight and volume. These diverse effects could also result in bone fracture tissue called osteoporosis (Lello et al., 2018; Sattar, 2016; Taylor et al., 2019). The Food and Drug Administration (FDA) approved OVX rat model to study menopause, postmenopausal osteoporosis and the possible natural and synthetic therapeutic agents (Johnston & Ward, 2015).…”